Injured Ghana international Jeffrey Schlupp will not make a comeback to action until March, according to coach Roy Hodgson.
He subsequently went under the knife, a procedure which extended his expected stay in the treatment room.
“A lot of teams can talk about the number of players they have injured at any one time, but a lot of those injuries are muscle injuries," Palace boss Roy Hodgson lamented, as reported by his club's official website.
“I think it’s very unusual to have as many as five players out, basically for the rest of the season.
“We already lost [Christian] Benteke for six weeks, [Wilfried] Zaha six weeks, Mamadou Sakho seven weeks, Schlupp eight to ten weeks.
"Five players out for the rest of the season – I think that’s a very unusual situation to find ourselves in.
"All of them are trauma injuries – none are due to muscle strains or pulls, they’re all cruciate ligaments, medial ligaments and fractures.”
Schlupp had been a key feature of Hodgson's set-up since the former England manager replaced Frank de Boer in September.
The 25-year-old has made 19 Premier League appearances, involving 18 starts, so far this season.
He joined The Eagles from Leicester City in January last year.